The mechanism controlling sequential synthesis of viral gene products and the regulations imposed on infected hot cells remain central problems in virology. Adenoviruses are particularly useful viruses for investigating these problems since they produce both lytic and defective infections, the family contains highly oncogenic and relaively nononcogenic members, they transform cells in vitro, they are important infectious agents in man, and they can be easily studied in the laboratory. Using temperature-sensitive mutants of oncogenic type 12 and nononcogenic type 5 adenoviruses regulation of viral replication, synthesis of host macromolecules, and transformation will be studied. The specific aim to elucidate the mechanisms regulating viral synthesis will also be pursued with the following models: 1) Defective replication of adenoviruses in African green monkey cells and the helper function of SV40; 2) the total dependence of adeno-associated viruses on adenoviruses; 3) in vitro synthesis of adenovirus proteins; and 4) regulation of transcription of early and late adenovirus mRNAs.